Expression Of PCDGF And VEGF In Esophageal Squamous Cell Carcinoma And Their Clinicopathologic Significance

Background and Objective:Esophageal carcinoma includes esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). It is a frequent malignant tumor of digestive canal, which is seriously threatening human health. Our country is a region of high incidence of esophageal carcinoma. ESCC occupies 90% of all esophageal carcinomas. Like other malignant tumors, its occurence and development is a complicated process including many steps and many factors. Once histiooytic phenotype develops malignant transformation, the formation of neogenetic vessels plays an important role in the process of tumor growth and metastasis. It is generally presumed that tumor neovascularity is one of the premises ensuring tumor growth and metastasis. So, the regulation mechanism of angiogenesis is a hot spot of the study of treatment and prevention of tumor constantly.The formation of new vessels is regulated by many factors. The up-regulation of growth factors or down-regulation of inhibition factors can both activate vascular endothelial cells being in resting state and trigger the "angiogenic switch". Vascular endothelial growth factor (VEGF) is one of the strongest promoting angiogenesis factors, which plays a critical role in the process of tumor angiogenesis. PC cell-derived growth factor (PCDGF or progranulin) is a latest discovered growth factors which are closely related to occurence, development and metastasis of epithelial cell derived tumors. Recent studies discovered that PCDGF could play the role of promoting tumor angiogenesis through up-regulating expression of VEGF. Adenocarcinoma always was taken as investigated object in the past. However, there was rare report about expression and biological function of PCDGF in squamous cell cancer so far. The vascular endothelial cells in tumor tissue were labeled by antibody to CD105 for counting microvessel density (MVD) in this experiment. Immunohistochemistry was used to detect expressions of MVD, PCDGF and VEGF. The experiment wanted to clarify the pathogenesy of ESCC through investigating the effect of PCDGF and VEGF in tumor angiogenesis.Methods:Immunohistochemistry S-P method was used to detect the differential expressions of PCDGF, VEGF and CD105 in 50 ESCC specimens and 20 normal esophageal mucosas from incisal edges in protein level. At the same time, we ascertained the location of their protein expressions.SPSS13.0 statistics software was used for statistical treatment.Results:1. The expression level of PCDGF was 94.0% (47/50) in cancer tissues. It was obviously higher than PCDGF expression level 40.0% (8/20), and the difference had statistical significance (P<0.001).2. The expression level of VEGF was 58.0% (29/50) in cancer tissues. It was obviously higher than VEGF expression level 25.0% (5/20) normal tissues, and the difference had statistical significance (P<0.01).3. The counted number of MVD in cancer tissues was 35.72±10.10 through specifically marked tumor neogenetic vessels by CD105. It was significantly higher than 16.31±6.74 of normal control tissues. The difference between the two had statistical significance (P<0.001).4. The expressed intensity of PCDGF had close correlation with histological grade of ESCC (P<0.01). Besides, it had significant positive correlation with infiltrating depth, lymph node metastasis and TNM staging of tumor (all P<0.05). However, it had no correlation with distant metastasis.5. The expression of VEGF had significant correlation with infiltrating depth, lymph node metastasis, distant metastasis and TNM staging of tumor (P<0. 05, P<0. 05, P<0. 05, P<0. 01). However, it had no correlation with histological grade.6. When the group of PCDGF (+++)/VEGF (+) (group A) compared with the group of PCDGF≤(++)/VEGF (+) or PCDGF (+++)/VEGF (-) (group B), the incidence of clinical pathology events indicating poor prognosis (lymph nodes metastasis, distant metastasis and TNM stages) had no significant difference. When the group of PCDGF≤(++)/VEGF (-) (group C) compared with group A and group B, the incidence of nodes metastasis was lower and TNM staging trended to morning stage (P<0.05 and P<0.001). However, incidence of distant metastasis had no significant difference.7. Both the expression of PCDGF and VEGF had positive correlation with MVD (r_s=0. 472 and r_s=0.436, P<0.01). Moreover, MVD was 44.18±11.07 in the group A, it was significantly higher than 34.84±6.08 in the group B and 28.00±5.52 in the group C (P<0.01 and P<0.001). And MVD was higher in group B than it in group C (P<0.05).8. The expression of PCDGF and VEGF in ESCC had significant positive correlation (all P<0. 05) through chi-square test (x~2=4.42) and Spearman rank correlation analysis (r_s=0.298).Conclusions:1. PCDGF has high expression in ESCC and it marks tumor tissues with high sensitivity and strong specificity. It can be a novel ESCC marker hopefully. The expression of PCDGF has positive correlation with tumor differentiation degree and TNM staging, which indicates that it may be related with development of ESCC.2. MVD in the group of both PCDGF and VEGF positive is significantly higher than it in the group of both PCDGF and VEGF negative. It indicates that both of them have close relationships with angiogenesis. They may take part in tumor growth, infiltration and metastasis through promoting tumor angiogenesis.3. MVD in the group of PCDGF (+++)/VEGF (+) is significantly higher thanother control groups. It indicates that the two may have cooperativity in controlling angiogenesis. The expression of PCDGF has significant positive correlation with the expression of VEGF. It can be inferred that PCDGF may affect tumor angiogenesis through regulating the expression of VEGF.4. Expression of VEGF and MVD has close correlation with infiltration and metastasis of ESCC, both can be important parameters reflecting tumor malignancy and prognosis.